Various platinum coordination compounds useful as anti-tumor agents are disclosed in co-pending application Ser. No. 405,184, filed Oct. 10, 1973 (which is a continuation application of application Ser. No. 230,533, filed Feb. 29, 1972, which is a continuation application of application Ser. No. 30,239, filed Apr. 20, 1970). Another class of platinum coordination compounds, i.e., malanato-platinum compounds, useful as anti-tumor agents are disclosed in co-pending application Ser. No. 260,989 (filed June 8, 1972). A method for the treatment of viral conditions utilizing platinum coordination compounds is disclosed in co-pending application Ser. No. 350,924, filed Apr. 13, 1973.
While extremely effective against a variety of tumors, the above-described platinum coordination compounds suffer from the disadvantages of (1) having a high level of renal toxicity, and (2) a low solubility in water. The latter characteristic renders the preparation of therapeutically useful compositions difficult.
It has been discovered that a certain class of platinum "blue" complexes have a high anti-tumor activity, are soluble in water, and have a low level of renal toxicity.
The prior art has long been aware of the so-called "platinblau" complexes. Credit for the discovery of "Platinblau", as these blue complexes were designated, is usually given to Hofmann and Bugge (Ber. 41: 312-314, 1908). They reacted Ag.sub.2 SO.sub.4 with the yellow platinum (II) coordination compound, Pt(CH.sub.3 CN).sub.2 Cl.sub.2 in aqueous solution and isolated a deep blue, amorphous material. It was thought to be monomeric in nature, containing platinum in the divalent state. Since this discovery only a few papers have appeared concerning further studies on "Platinblau" and similar blue products. Gillard and Wilkinson (J. Chem. Soc., 2835-37, 1964) postulated that "Platinblau" had the empirical formula Pt(CH.sub.3 CONH).sub.2.H.sub.2 O with polymeric chains, bridging acetamide groups, and divalent platinum. Brown et al. (J.A.C.S. 91:11: 2895-2902, 1969 and 90:20: 5621-5622, 1968) have attempted to demonstrate that it is a platinum (IV) complex containing chelating acetamide ligands, and hydroxyl groups in the other two coordination positions. We have found that both blue and purple products could be isolated from the "Platinblau" reaction, with the purple species being the more highly oxidized (vide infra). Thus, there is considerable controversy over the exact nature of this complex. Brown et al (ibid.) have also reported the preparation of highly colored amide complexes of platinum by heating, for example, trimethylacetamide and either Pt(CH.sub.3 CN).sub.2 Cl.sub.2 or K.sub.2 [PtCl.sub.4 ] (a reddish colored salt). From this reaction three components were identified by chromatography. These were two yellow crystalline materials and a blue amorphous powder. Although they reported that they could not identify any of these blue products in a positive manner, they postulated that the blue material contained tetravalent platinum, which bidentate anide anions and chloride ligands completing the coordination sphere.
The only other reference to anomalously colored platinum compounds containing cis-amino groups as ligands rather than amides is that concerning mixture of cis-dichlorodiammineplatinum (II) and sulfuric acid (Gillard et al, ibid.). Crystals of this blue black material were obtained and a preliminary X-ray diffraction study showed that the Pt-Pt distance was 3.06 .ANG., suggesting strong interaction. They concluded that this complex contained layers of cis-dichlorodiammineplatinum (II) held together by Pt-Pt bonds, with the sulfate ion hydrogen bonded to the coordinated ammonia groups.